A clinical audit of the utilisation of red cell products in elective total hip replacement surgery

Background. Previous studies have documented a marked variation in transfusion practice for total hip replacement (THR) surgery.Objective. To audit red cell product utilisation for THR at two Western Cape tertiary referral hospitals (HY and HG).Methods. The folders of 207 consecutive patients undergoing elective THR surgery from January 2013 to December 2013 were reviewed. Information relating to age, sex, clinical observations, indications for surgery, pre- and postoperative haemoglobin (Hb) values, comorbidities, length of hospital stay and transfusion history was recorded.Results. The transfusion rate at HY (41.6%) was significantly higher than that at HG (10.0%). The mean postoperative Hb in the transfused patients at HG was 8.3 g/dL v. 9.1 g/dL at HY. Females had a significantly higher transfusion rate (33.0%) than males (15.0%) (p<0.05), and the mean age of transfused patients was significantly greater than that of untransfused patients (p<0.005). Although patients with comorbidities had a higher transfusion rate than those without, this did not reach statistical significance. Of 120 patients with complete data, 113 (94.2%) had a blood bank order, of which the vast majority, 102/113 (90.3%), were group-and-screen (G&S) requests; 29/113 (25.7%) were converted to a full crossmatch.Conclusions. Overall, the transfusion rate for both hospitals was 25.8%, which is well within published rates. A guideline Hb trigger of 8.0 g/dL is recommended as per published guidelines, with the caveat that the clinical judgement of the attending clinician whether a transfusion is indicated is paramount. Causes of preoperative anaemia should be investigated and treated. Routine cross-matching preoperatively is unnecessary, and a G&S order is sufficient

Monocyte derived dendritic cells have reduced expression of co-stimulatory molecules but are able to stimulate autologous T-cells in patients with MDS

Introduction: Research has implied that the immune system plays a role in the pathogenesis of MDS and that T-cells are reacting to tumour antigen present on the surface of the malignant cells. This could imply that the immune system could be utilized to generate immune based therapy. The aim of this pilot study was to examine the feasibility of studying this further by analysing the interaction of dendritic cells with T-cells in a small cohort of MDS patients. Methods: Dendritic cells were generated in 6 MDS patients and 9 controls by culturing monocytes with GM-CSF and IL-4. After activation with LPS and TNFα, the dendritic cells were analyzed for expression of co-stimulatory and activation antigens. Thereafter, they were co-cultured with T-cells and the T-cell response was examined by measuring the % change in expression of the activation antigen CD69. Results: MDS MoDC had reduced expression of HLA-DR (p=0.006), CD11c (p=0.0004), CD80 (p=0.03) and CD86 (p=0.003), while resting T-cells from MDS patients had higher expression of the activation antigen CD69 on all subsets. The % change in CD69 expression increased significantly for both the control and MDS T-cells after co-culture with allogeneic dendritic cells, however this change was lower in the MDS group. Despite the increased CD69 expression prior to culture, MDS MoDC significantly up-regulated CD69 expression on autologous T-cells to values that were statistically higher than control cells. Conclusion: This initial study suggests that the T-cells in MDS are able to respond to dendritic cells and are therefore probably not part of the malignant clone. It further implies that the dendritic cell population could be capable of presenting antigen and initiating an immune response and therefore further study is both feasible and warranted

The relationship between immunogenic red blood cell antigens and Human Immunodeficiency Virus infection

Introduction: Evidence suggests that red cell antigens may act as receptors for viruses and bacteria andtherefore could be associated with HIV infection. Previous studies have been controversial and thereforethe aim of this exploratory study was to analyse the expression of immunogenic red cell antigens inHIV-seropositive individuals and to compare the results to negative donors from South Africa.Methods: The expression of ABO, Rh, Kell and Duffy antigens from 119 HIV-seropositive patients wascompared to 317 HIV-seronegative blood donors. Nucleic acid amplification testing and PCR were usedto determine the HIV status and the ID-Gel Card Technology was used to determine the blood groupantigen profile.Results: There was no significant difference in the expression of A, B, AB, Duffy or Kel antigens betweenthe two groups but significantly lower numbers of HIV+ individuals were O Rh Negative (p = ,0.0001).Analysis of those with a Duffy null phenotype revealed a significantly higher incidence of blood type ARH1-Positive, Dce/R0r and B RH1-Positive, DcEe/R2r within the HIV-seropositive group (p = < 0.05). Noneof the HIV-seropositive individuals were O RH1-Negative, dce/rr.Conclusion: In conclusion these initial findings have demonstrated a decreased incidence of blood type ORh1-negative in HIV + individuals which suggests that red blood cell antigens may play an important rolein susceptibility to HIV infection. The relationship between red cell antigens and HIV infection howeverremains complex and therefore larger studies are required to confirm these results

Do Blood Group Antigens and the Red Cell Membrane Influence Human Immunodeficiency Virus Infection?

The expression of blood group antigens varies across human populations and geographical regions due to natural selection and the influence of environment factors and disease. The red cell membrane is host to numerous surface antigens which are able to influence susceptibility to disease, by acting as receptors for pathogens, or by influencing the immune response. Investigations have shown that Human Immunodeficiency Virus (HIV) can bind and gain entry into erythrocytes, and therefore it is hypothesized that blood groups could play a role in this process. The ABO blood group has been well studied. However, its role in HIV susceptibility remains controversial, while other blood group antigens, and the secretor status of individuals, have been implicated. The Duffy antigen is a chemokine receptor that is important in the inflammatory response. Those who lack this antigen, and type as Duffy null, could therefore be susceptible to HIV infection, especially if associated with neutropenia. Other antigens including those in the Rh, Lutheran and OK blood group systems have all been shown to interact with HIV. More recently, experiments show that cells which overexpress the Pk antigen appear to be protected against infection. These reports all demonstrate that red cell antigens interact and influence HIV infection. However, as the red cell membrane is complex and the pathogenesis of HIV multi-factorial, the role of blood group antigens cannot be studied in isolation

Leucocyte Telomere Length and Glucose Tolerance Status in Mixed-Ancestry South Africans

Telomeres are DNA-tandem repeats situated at the ends of chromosomes and are responsible for genome stabilization. They are eroded by increased cell division, age and oxidative stress with shortened leucocyte telomeres (LTL) being associated with inflammatory disorders, including Type II diabetes. We assessed LTL in 205 participants across glucose tolerance groups at baseline and after three years in the mixed ancestry population of South Africa which have been shown to have high rates of obesity and T2DM. Baseline and follow-up data included glucose tolerance status, anthropometric measurements, lipids, insulin, &#947;-glutamyl transferase (GGT), cotinine, and HbA1c. Telomere length was measured using the absolute telomere q-PCR method performed on a Bio-Rad MiniOpticon Detector. No significant difference was detected in LTL across glucose tolerance groups at both time points, including in subjects who showed a deterioration of their glucose tolerance status. There was, however, a significant negative correlation between LTL and age which was more pronounced in diabetes (r = &#8722;0.18, p = 0.04) and with GGT (r = &#8722;0.16, p = 0.027). This longitudinal study has demonstrated that LTL shortening is not evident within three years, nor is it associated with glycaemia. Further studies in a larger sample and over a longer time period is required to confirm these results

Platelet, monocyte and neutrophil activation and glucose tolerance in South African Mixed Ancestry individuals

Platelet activation has been described in patients with chronic inflammation, however in type 2 diabetes mellitus it remains controversial. We compared levels of platelet leucocyte aggregates, monocyte and granulocyte activation across glucose tolerance statuses in mixed ancestry South Africans. Individuals (206) were recruited from Bellville-South, Cape Town, and included 66% with normal glucose tolerance, 18.7% pre-diabetes, 8.7% screen-detected diabetes and 6.3% known diabetes. Monocyte and neutrophil activation were measured by calculating the percentage of cells expressing CD142 and CD69 while platelet monocyte aggregates were defined as CD14++ CD42b+ events and platelet neutrophil aggregates as CD16++ CD42b+ events. The percentage of monocytes and neutrophils expressing CD69 and CD142 was significantly higher in known diabetes and prediabetes, but, lowest in screen-detected diabetes (both p≤0.016). The pattern was similar for platelet monocyte and neutrophil aggregates (both p≤0.003). In robust linear regressions adjusted for age and gender, known diabetes was significantly and positively associated with the percentage of monocytes expressing CD69 [beta 11.06 (p=0.016)] and CD42b (PMAs) [19.51 (0.003)] as well as the percentage of neutrophils expressing CD69 [14.19 (<0.0001)] and CD42b [17.7 (0.001)]. We conclude that monitoring platelet activation in diagnosed diabetic patients may have a role in the management and risk stratification

The Relationship between the Oral Microbiota and Metabolic Syndrome

The oral microbiota plays a crucial role in both systemic inflammation and metabolic syndrome (MetS), which is characterised by low-grade inflammation. Studies have analysed the gut microbiota using stool specimens from subjects with MetS; however, the etiological role of the oral microbiota in the development of MetS is still uncertain. We investigated the oral microbiota of 128 subgingival plaque samples from a South African cohort with and without MetS. After a comprehensive analysis of the oral microbiota, we observed a significant increase in Gram-positive aerobic and anaerobic microbiota in those with MetS. We observed an abundance of Actinomyces, Corynebacterium, and Fusobacterium genera in the MetS group, which differed significantly from previous studies, which found Granulicatella to be enriched in MetS. To further assess the impact of the metabolic parameters (FBG, Waist C, HDL, TGs, and BP) on the oral microbiota, we calculated the odds ratio (ORs) for significant oral microbiota identified between the MetS groups. We found that different species were associated with at least four MetS risk factors. This study has shown that the oral microbiota is disrupted in MetS and may promote inflammation providing a gateway to other systemic diseases, including diabetes and cardiovascular diseases

MicroRNAs-1299, -126-3p and -30e-3p as Potential Diagnostic Biomarkers for Prediabetes

This cross-sectional study investigated the association of miR-1299, -126-3p and -30e-3p with and their diagnostic capability for dysglycaemia in 1273 (men, n = 345) South Africans, aged &gt;20 years. Glycaemic status was assessed by oral glucose tolerance test (OGTT). Whole blood microRNA (miRNA) expressions were assessed using TaqMan-based reverse transcription quantitative-PCR (RT-qPCR). Receiver operating characteristic (ROC) curves assessed the ability of each miRNA to discriminate dysglycaemia, while multivariable logistic regression analyses linked expression with dysglycaemia. In all, 207 (16.2%) and 94 (7.4%) participants had prediabetes and type 2 diabetes mellitus (T2DM), respectively. All three miRNAs were significantly highly expressed in individuals with prediabetes compared to normotolerant patients, p &lt; 0.001. miR-30e-3p and miR-126-3p were also significantly more expressed in T2DM versus normotolerant patients, p &lt; 0.001. In multivariable logistic regressions, the three miRNAs were consistently and continuously associated with prediabetes, while only miR-126-3p was associated with T2DM. The ROC analysis indicated all three miRNAs had a significant overall predictive ability to diagnose prediabetes, diabetes and the combination of both (dysglycaemia), with the area under the receiver operating characteristic curve (AUC) being significantly higher for miR-126-3p in prediabetes. For prediabetes diagnosis, miR-126-3p (AUC = 0.760) outperformed HbA1c (AUC = 0.695), p = 0.042. These results suggest that miR-1299, -126-3p and -30e-3p are associated with prediabetes, and measuring miR-126-3p could potentially contribute to diabetes risk screening strategies

Circulating miR-30a-5p and miR-182-5p in prediabetes and screen-detected diabetes mellitus

CITATION: Weale C. J. et al. 2020. Circulating miR-30a-5p and miR-182-5p in Prediabetes and Screen-Detected Diabetes Mellitus. Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 13:5037-5047. doi:10.2147/DMSO.S286081The original publication is available at https://www.dovepress.com/diabetes-metabolic-syndrome-and-obesity-targets-and-therapy-journalBackground: microRNAs (miRNAs) have been touted as potential diagnostic and prognostic biomarkers for various diseases. The aim of the present study was to evaluate the diagnostic value of miR-30a-5p and miR-182-5p for prediabetes and screen-detected type 2 diabetes mellitus (T2DM). Methods: The study included 1270 participants (207 prediabetes, 94 screen-detected diabetes and 969 normotolerant) from the Vascular and Metabolic Health (VMH) study. Whole blood levels of miR-30a-5p and miR-182-5p were quantitated by RT-qPCR. Multivariable logistic regressions were used to relate miRNAs with prediabetes or T2DM and receiver operating characteristic (ROC) curves were used to evaluate the ability of each miRNA to diagnose these conditions. Results: Both miRNAs were significantly highly expressed in individuals with prediabetes or T2DM (both ≥3.2-fold, and p<0.001). We also observed significant under-expression in T2DM relative to prediabetes for miR-182-5p (0.49-fold, p=0.001). Age, sex and BMI-adjusted partial correlation coefficient analysis revealed a significant correlation between the two miRNAs across glucose tolerance statuses (r≥0.932, p<0.001). In normotolerant individuals, both miRNAs showed a negative correlation with waist circumference and positive correlation with HDL-cholesterol whilst in T2DM they correlated positively with hip circumference, 2-hour insulin, HDL- and LDL-cholesterol. Multivariable logistic regressions revealed both miRNAs to be consistently and continuously associated with prediabetes or T2DM (OR≥1.18, 95% 95% CI: 1.10-1.28, p<0.001), while only miR-182-5p associated with a reduced prevalence of T2DM relative to prediabetes (OR: 0.89, 95% CI: 0.83-0.96, p=0.003). In ROC analyses, miR-182-5p almost outperformed HbA1c in diagnosing prediabetes; area under the curve 0.74 vs 0.69. Conclusion: Our findings demonstrate that miR-30a-5p and miR-182-5p are associated with dysglycaemia and could potentially predict prediabetes, particularly miR-182-5p.https://www.dovepress.com/circulating-mir-30a-5p-and-mir-182-5p-in-prediabetes-and-screen-detect-peer-reviewed-fulltext-article-DMSOPublishers versio